Posted by Sara Fazio • September 13th, 2013

Cryoglobulins are present in about a quarter of patients with hepatitis C; in some, cryoglobulinemia can become symptomatic or even life-threatening. The latest article in our Current Concepts review series summarizes evolving therapy for the disorder, including new therapeutic options that are becoming available.

Cryoglobulins are immunoglobulins characterized by their insolubility at low temperatures and their dissolution after rewarming to body temperature. On the basis of their immunochemical composition, cryoglobulins are classified as either single (type I), consisting of a monoclonal immunoglobulin, or mixed, comprising two or more immunoglobulin isotypes, with (type II) or without (type III) a monoclonal component.

Clinical Pearls

• What is the relationship between cryoglobulinemia and hepatitis C virus?

In the early 1990s, it became evident that more than 90% of patients with mixed cryoglobulinemia were infected with hepatitis C virus (HCV). Cryoglobulins can be detected in 25 to 30% of HCV-positive patients, but in asymptomatic cases, treatment is unnecessary.

• In patients with HCV and cryoglobulinemic vasculitis, what factors are predictive of a poor response to peginterferon alpha and ribavirin?

Morning Report Questions

Q:When should rituximab be considered for patients with cryoglobulinemic vasculitis?

A: Whether rituximab should be administered to patients with cryoglobulinemic vasculitis as first- or second-line therapy remains to be determined. On the basis of clinical evidence from uncontrolled and nonrandomized studies, the combination of peginterferon alfa and ribavirin as first-line therapy is recommended for patients with mild-to-moderate disease activity, although peginterferon alfa may exacerbate some of the clinical features of cryoglobulinemic vasculitis, such as skin ulcers and peripheral neuropathy. However, for patients with active disease that is resistant to the antiviral agents, as well as for patients with life-threatening cryoglobulinemic vasculitis, the addition of rituximab or other B-cell-depleting monoclonal antibodies can restrain the clonal expansion of a rheumatoid factor-producing B-cell subset. This form of triple therapy should be accompanied or augmented by plasmapheresis and immunosuppressive therapy.

Q:What is the role for double filtration plasmapheresis in cryoglobulinemic vasculitis?

A: Therapeutic apheresis, a procedure generally performed for palliative purposes, can be useful in the treatment of patients with cryoglobulinemic vasculitis who have a hyperviscosity syndrome. The underlying rationale is the possibility of removing both the cryoprecipitating proteins and the viral particles. Although multicenter, randomized studies comparing plasma exchange with either placebo or immunosuppressive therapy are still lacking, strikingly positive results have been reported. In particular, double-filtration plasmapheresis allows the selective removal of pathogenic substances from plasma while preserving other, essential components. Candidates for double-filtration plasmapheresis are patients with late, refractory-stage cryoglobulinemic vasculitis, as well as those with earlier disease stages. The procedure can be used alone or in combination with antiviral therapy.